Defecation of a “colon cast” as a rare presentation of acute graft-versus-host disease

Diffuse involvement of the gastrointestinal tract by graft versus host disease (GVHD) is a common complication of allogeneic hematopoietic stem cell transplant (HSCT). Gastrointestinal GVHD usually presents 3 or more weeks after HSCT and is characterized by profuse diarrhea, anorexia, nausea, vomiting, abdominal pain and gastrointestinal bleeding. We report a case of a 23-year-old male who had undergone allogeneic HSCT and presented with bloody diarrhea on the 90th day post-HSCT. On the fourth day of admission, the patient passed per rectum a 27-cm long pinkish colored fleshy material recognized as a “colon cast”. Sigmoidoscopy showed a congested and erythematous rectum with the remaining portion of the “colon cast” attached to the proximal part of the sigmoid colon. A biopsy from the rectal wall was suggestive of grade IV GVHD. The patient was treated with methylprednisolone, cyclosporin and mycophenolate mofetil, with a partial response (diarrhea and abdominal pain improved), but then he developed multiple other medical complications and died after 3 months.

A cute graft-versus-host disease (GVHD) oc-curs after allogeneic hematopoietic stem cell transplantation (HSCT) as a consequence of an immune reaction by the donor immune cells against host tissues. About 35% to 50% of HSCT recipients develop acute GVHD. 1,2 Clinically, the diagnosis is suspected when a recipient of HSCT develops any or all of the following signs or symptoms: dermatitis (skin rash), cutaneous blisters, crampy abdominal pain with or without diarrhea, persistent nausea and vomiting, or hepatitis (with elevation of bilirubin and/or liver enzymes). 3 Typically, these symptoms occur before day 100 after the HSCT, but may occur later. 4 The spontaneous passage of a full-thickness colon cast has been described eight times previously, [5][6][7][8][9] includ-ing one case of a mucosal cast. In five cases the etiology was occlusion of the mesenteric artery. In the remaining three cases, one patient had pancreatitis, the other had undergone resection of a lower rectal carcinoma with a sigmoid pouch-anal anastomosis and ileostomy, and the last had undergone Hartmann' s procedure sacrific-ing the inferior mesenteric artery for a perforated diver-ticulum and pelvic abscess. [5][6][7][8][9] To our knowledge, there

Defecation of a "colon cast" as a rare presentation of acute graft-versus-host disease
Hamad Al Ashgar, a Musthafa Peedikayil, a Naeem Chaudhri, b Abdulmonem Al-Ghamdi c Diffuse involvement of the gastrointestinal tract by graft versus host disease (GVHD) is a common com-plication of allogeneic hematopoietic stem cell transplant (HSCT). Gastrointestinal GVHD usually pres-ents 3 or more weeks after HSCT and is characterized by profuse diarrhea, anorexia, nausea, vomiting, abdominal pain and gastrointestinal bleeding. We report a case of a 23-year-old male who had under-gone allogeneic HSCT and presented with bloody diarrhea on the 90th day post-HSCT. On the fourth day of admission, the patient passed per rectum a 27-cm long pinkish colored fleshy material recognized as a "colon cast". Sigmoidoscopy showed a congested and erythematous rectum with the remaining portion of the "colon cast" attached to the proximal part of the sigmoid colon. A biopsy from the rectal wall was suggestive of grade IV GVHD. The patient was treated with methylprednisolone, cyclosporin and mycophenolate mofetil, with a partial response (diarrhea and abdominal pain improved), but then he developed multiple other medical complications and died after 3 months.
are no reports of spontaneous passage of a colon cast in the context of acute GVHD.

Case
A 23-year-old male underwent allogeneic HSCT for aplastic anemia 90 days prior to presentation. The pa-tient presented to the emergency department with a history of severe lower abdominal pain, bloody diarrhea and fever of 3-days duration. He was discharged from the hospital a few days prior to this presentation after recovering from multiple medical problems following HSCT including E coli and Streptococcus viridans sept t ticemia, febrile neutropenia, cytomegalovirus (CMV) antigenemia, GVHD involving the skin, and aspergil-losis of the lung. On admission the patient was febrile and appeared pale. The skin was hyperpigmented from GVHD. The oral cavity showed features of mucositis. The lower abdomen was tender on palpation. The car-diovascular, respiratory and nervous system examina-tion was unremarkable. Broad-spectrum antibiotics and other supportive measures were begun and the patient was moved to the intensive care unit. On the fourth day of admission the patient passed a 27-cm long, tubular,   pinkish-colored fleshy material rectally (Figure 1). This structure was recognized as a "colon cast" and was sent to pathology for histology. The stool examination for culture and sensitivity of Clostridium difficle was nega-tive. A CT scan of the abdomen showed non-specific thickening of the large and small bowel including rec-tum as well as inflammation of the surrounding of the mesenteric fat. A sigmoidoscope was unable to pass more than 25 cm from the anal verge. The sigmoid and rectal mucosa was congested and erythematous. At 25 cm from the anal verge, the residual part of the "colon cast" was seen attached to the colonic wall.
The patient was treated for acute GVHD with meth-ylprednisolone, cyclosporine and tacrolimus. He was lat-er treated with mycophenolate mofetil and anti-thymo-cyte globulin as per our hospital protocol. Appropriate antibiotics, hydration and other supportive measures were also given. The patient showed some response to treatment with a reduction in the amount of diarrhea. Unfortunately, the patient developed multiple complica-tions afterwards, including gram-negative sepsis, CMV infection, and aspergillosis of the lung, progressive pan-cytopenia and graft failure. The patient died in the hospi-tal due to multi-organ failure 3 months after admission.

DisCussion
About 35% to 50% of HSCT recipients will develop acute GVHD. 10 Acute GVHD is a clinical diagnosis, but other conditions can mimic or coexist with GVHD, such as drug toxicity and infections. Therefore, a biopsy is recommended to confirm clinical suspicion whenever possible. 11 The pathophysiology of acute GVHD is a complex process. Patients who undergo bone marrow trans-plantation receive high-dose chemotherapy before the procedure. High-dose chemoradiotherapy damages the host tissues causing release of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha and inter-leukin 1, which lead to activation of host antigen-pre-senting cells. The donor T-cells recognize alloantigens on host antigen-presenting cells and activate the donor T-cells. The activated T-cells then proliferate and dif-ferentiate into effector cells and secrete cytokines such as interferon (IFN)-gamma. TNF-alpha and IFNgamma cause further injury to the gastrointestinal epi-thelium leading to the tissue damage characteristic of acute GVHD. 12 The gastrointestinal system is the third most com-mon organ involved in acute GVHD. Gut GVHD may involve any part of the gastrointestinal tract and is frequently the most severely involved organ. It is often difficult to treat gut GVHD. Diarrhea and abdominal cramping are generally the hallmarks of gut involve-ment. Clinical manifestations of gut GVHD include diarrhea, nausea, vomiting and crampy abdominal pain. There may be a large volume of diarrhea, which is often bloody. Abdominal distention and paralytic ileus may develop. 13 Many of the gastrointestinal symptoms are nonspecific and hence endoscopic biopsy confirmation is often needed.
Upper and lower gastrointestinal endoscopy is a useful modality to diagnose acute GVHD and to dif-ferentiate it from other causes of diarrhea. Endoscopic findings of gut GVHD may vary from normal to exten-sive edema, mucosal sloughing or diffuse bleeding from the gut mucosa. The endoscopy may show prominent lesions in the cecum, ileum, and ascending colon. The mucosa involvement can be seen in the stomach, duo-denum, and rectum as well. 13 Endoscopy is a useful tool to grade the severity of acute GVHD, helping the physician to choose appro-priate treatment and to predict prognosis. Endoscopic grading is based on the appearance of colonic mucosa during colonoscopy or sigmoidoscopy. Endoscopically, acute GVHD can be classified as stage 1 to 4. Stage 1 is normal appearing mucosa, stage 2 will show a loss of vascular marking of normal colonic vascular pattern or there will be focal mild erythema. Stage 3 acute GVHD will have colonic mucosal edema, erythema, erosions, and/or bleeding. Stage 4 is characterized by colonic ul-ceration and bleeding. 14 The biopsy is also highly useful for assessing the severity of acute GVHD. Histological grading of GVHD is also divided into 4 classes. Grade 1 GVHD is characterized by increased crypt apoptosis; grade 2 with apoptosis and crypt abscess; grade 3 with individual crypt necrosis; and grade 4 by total denuda-tion of areas of the mucosa. 15 According to the above classification of assessment of severity of gut GVHD, this patient had stage 4 and grade 4 acute GVHD.
To our knowledge, passage of the colonic cast as a manifestation of acute GVHD has never been report-ed. Previously, one case was reported in the literature, with passage of esophageal mucosal cast as a complica-tion of chronic GVHD following bone marrow trans-plantation. 16 We propose that the colon mucus cast in this patient was the result of severe GVHD, leading to a total denudation of the mucosa from the deeper lay-ers of the colonic wall.